Adaptive Immunity Chapter 7 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.

2 Adaptive Immunity Works together with innate immunity, aka inflammation Works together with innate immunity, aka inflammation Specificity Specificity Each T or B cell recognizes only one antigen, but together a group of T and B cells recognize a host of foreign antigens Each T or B cell recognizes only one antigen, but together a group of T and B cells recognize a host of foreign antigens Memory Memory Confers long-term protection Confers long-term protection

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 3 End Products of Adaptive Immunity Lymphocytes (cellular immunity): T and B cells Lymphocytes (cellular immunity): T and B cells Antibody (humoral immunity): immune globulins Antibody (humoral immunity): immune globulins

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 4 Adaptive Immunity Clonal diversity Clonal diversity Production of T and B lymphocytes Production of T and B lymphocytes Antigen recognition Antigen recognition Lymphocyte specificity Lymphocyte specificity Clonal selection Clonal selection Antigen processed and presented to immune cells by APCs Antigen processed and presented to immune cells by APCs Cellular interaction of T cells and APCs Cellular interaction of T cells and APCs

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 7 Types of Immunity Natural immunity Natural immunity Active immunity Active immunity Passive immunity Passive immunity

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 8 Humoral and Cell-Mediated Immunity The cellular and humoral responses are not independent The cellular and humoral responses are not independent Humoral immunity Humoral immunity Fluid immunity Fluid immunity Circulating antibody Circulating antibody Cell-mediated immunity Cell-mediated immunity T cell differentiation T cell differentiation

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 9 Active vs. Passive Immunity Active immunity Active immunity Antibodies or T cells produced after either a natural exposure to an antigen or after immunization Antibodies or T cells produced after either a natural exposure to an antigen or after immunization Passive immunity Passive immunity Preformed antibodies or T lymphocytes are transferred from a donor to a recipient Preformed antibodies or T lymphocytes are transferred from a donor to a recipient

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 10 Recognition and Response Required for a successful immune response Required for a successful immune response Clusters of differentiation (CD) Clusters of differentiation (CD) Originally used to describe proteins found on the surface of lymphocytes Originally used to describe proteins found on the surface of lymphocytes Now it is a labeling system used to identify a family of proteins on many cells Now it is a labeling system used to identify a family of proteins on many cells

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 11 Antigen A molecule that can react with (or be recognized by) the immune system A molecule that can react with (or be recognized by) the immune system Recognized as nonself Recognized as nonself Pathogens (viruses, bacteria, fungi, etc.) Pathogens (viruses, bacteria, fungi, etc.) Bee venom Bee venom Pollen Pollen Foods Foods Tissue Tissue Blood products Blood products

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 12 Recognition and Response Antigens vs. immunogens Antigens vs. immunogens Antigen (Ag): a molecule that binds and reacts with antibody (Ab) or lymphocyte receptors Antigen (Ag): a molecule that binds and reacts with antibody (Ab) or lymphocyte receptors Immunogen: an Ag that can trigger an immune response Immunogen: an Ag that can trigger an immune response

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 13 Self-Antigen and Tolerance Degree of foreignness to host Degree of foreignness to host Most important Most important Size Size Small molecular weight Ags called haptens; cant trigger immune response themselves but can when bound to a carrier protein Small molecular weight Ags called haptens; cant trigger immune response themselves but can when bound to a carrier protein Chemical complexity Chemical complexity Amount Amount

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 14 Self-Antigen and Tolerance Tolerance: we recognize ourselves as not foreign Tolerance: we recognize ourselves as not foreign Central tolerance: lymphocytes with receptors against self-antigens are eliminated Central tolerance: lymphocytes with receptors against self-antigens are eliminated Peripheral tolerance: prevents recognition by lymphocytes and Abs Peripheral tolerance: prevents recognition by lymphocytes and Abs

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 15 Antigen Presentation Antigen-presenting cells (APCs) Antigen-presenting cells (APCs) Major histocompatibility complex (MHC) Major histocompatibility complex (MHC) Glycoproteins on the surface of all human cells (except RBCs) Glycoproteins on the surface of all human cells (except RBCs) Also called human leukocyte antigens (HLAs) Also called human leukocyte antigens (HLAs) MHC class I molecules MHC class I molecules A, B, and C A, B, and C MHC class II molecules MHC class II molecules DR, DP, and DQ DR, DP, and DQ MHC class III molecules MHC class III molecules

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 16 Molecules That Present Antigen Ag is processed within cells Ag is processed within cells Expressed on the cell surface in a specific manner Expressed on the cell surface in a specific manner Some Ags need special APCs; others can be processed by most any cell type Some Ags need special APCs; others can be processed by most any cell type

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 18 Transplantation Cells in transplanted tissue from one individual have a different set of MHC surface antigens than those of recipient Cells in transplanted tissue from one individual have a different set of MHC surface antigens than those of recipient Thus recipient can mount an immune response against foreign MHC molecules Thus recipient can mount an immune response against foreign MHC molecules Haplotype Haplotype Combination of A, B, C, DR, DQ, and DP alleles Combination of A, B, C, DR, DQ, and DP alleles

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 19 Tissue/Organ Transplantation Inheritance of human leukocyte antigens (HLAs) (synonym for MHC molecules) Inheritance of human leukocyte antigens (HLAs) (synonym for MHC molecules)

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 20 CD1 Antigen-presenting molecules Antigen-presenting molecules Found on antigen-presenting and thymus cells Found on antigen-presenting and thymus cells Present lipid antigens Present lipid antigens Mycobacterium, tuberculosis Mycobacterium, tuberculosis

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 21 Antigen Recognition Antigen is directly recognized by circulating antibody, antigen receptors on B cells (BCR), and T lymphocytes (TCR) Antigen is directly recognized by circulating antibody, antigen receptors on B cells (BCR), and T lymphocytes (TCR)

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 22 Antibodies Also called immunoglobulins Also called immunoglobulins Produced by plasma cells Produced by plasma cells Classes of antibody Classes of antibody IgG, IgA, IgM, IgE, and IgD IgG, IgA, IgM, IgE, and IgD Characterized by antigenic, structural, and functional differences Characterized by antigenic, structural, and functional differences

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 23 Molecules That Recognize Antigen Antibodies: classes of immunoglobulins Antibodies: classes of immunoglobulins

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 24 Molecules That Recognize Antigen B-cell receptor complex: antibodies and accessory molecules B-cell receptor complex: antibodies and accessory molecules

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 25 Antibodies Protein Protein Part of the adaptive immune response that interacts with antigen Part of the adaptive immune response that interacts with antigen Usually classes of immunoglobulins Usually classes of immunoglobulins

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 26 Antibody Structure Antigen-binding fragment (Fab) Antigen-binding fragment (Fab) Recognition sites (receptors) for antigenic determinants Recognition sites (receptors) for antigenic determinants Crystalline fragment (Fc) Crystalline fragment (Fc) Responsible for biologic function Responsible for biologic function Polypeptide chains (4) Polypeptide chains (4) Light chains (2) and heavy chains (2) Light chains (2) and heavy chains (2)

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 27 Antigen Binding Amino acid sequences of the variable regions of the heavy and light chains Amino acid sequences of the variable regions of the heavy and light chains Framework regions control antibody folding Framework regions control antibody folding Lock and key Lock and key Noncovalent chemical interactions Noncovalent chemical interactions Antibody valence Antibody valence IgG, IgD, and IgE2 IgG, IgD, and IgE2 IgA4 IgA4 IgMtheoretically 10, likely 5 IgMtheoretically 10, likely 5

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 31 Immunoglobulin M (IgM) Largest of the immunoglobulins Largest of the immunoglobulins Pentamer stabilized by a J-chain Pentamer stabilized by a J-chain First antibody produced during the primary response to an antigen First antibody produced during the primary response to an antigen Synthesized during fetal life Synthesized during fetal life

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 33 Immunoglobulin G (IgG) Most abundant class (80%-85%) Most abundant class (80%-85%) Transported across the placenta Transported across the placenta Four classes Four classes IgG1, IgG2, IgG3, and IgG4 IgG1, IgG2, IgG3, and IgG4

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 35 Secretory (Mucosal) Immune System Lymphoid tissues that protect the external surfaces of the body Lymphoid tissues that protect the external surfaces of the body Antibodies present in tears, sweat, saliva, mucus, and breast milk Antibodies present in tears, sweat, saliva, mucus, and breast milk IgA is the dominant immunoglobulin IgA is the dominant immunoglobulin Small numbers of IgG and IgM are present Small numbers of IgG and IgM are present

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 36 Immunoglobulin A (IgA) Two classes Two classes IgA1 molecules: predominantly in the blood IgA1 molecules: predominantly in the blood IgA2 molecules: predominantly in normal body secretions IgA2 molecules: predominantly in normal body secretions IgAs in body secretions are dimers anchored by J-chain and secretory piece IgAs in body secretions are dimers anchored by J-chain and secretory piece Secretory piece may function to protect IgAs against enzyme degradation Secretory piece may function to protect IgAs against enzyme degradation

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 38 Immunoglobulin E (IgE) Least concentrated of the immunoglobulin classes in the circulation Least concentrated of the immunoglobulin classes in the circulation Mediator of many common allergic responses Mediator of many common allergic responses Fc portions of IgEs are bound to mast cells Fc portions of IgEs are bound to mast cells Defender against parasites Defender against parasites

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 41 Immunoglobulin D (IgD) Limited information on IgD function Limited information on IgD function Low concentration in the blood Low concentration in the blood Located primarily on the surface of developing B lymphocytes Located primarily on the surface of developing B lymphocytes Function as one type of B cell antigen receptor Function as one type of B cell antigen receptor

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 42 T-Cell–Receptor Complex Antibody-like transmembrane protein (TCR) Antibody-like transmembrane protein (TCR) Accessory proteins for intracellular signaling Accessory proteins for intracellular signaling Referred to as CD3 Referred to as CD3 T-cell–receptor complex: transmembrane proteins and accessory proteins T-cell–receptor complex: transmembrane proteins and accessory proteins

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 43 B-Cell–Receptor Complex Located on surface of B cells Located on surface of B cells Consists of: Consists of: Antigen-recognition molecules Antigen-recognition molecules Monomer IgM and IgD Monomer IgM and IgD Accessory intracellular-signaling molecules Accessory intracellular-signaling molecules Ig-alpha and Ig-beta heterodimers Ig-alpha and Ig-beta heterodimers

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 44 Generation of Clonal Diversity All necessary receptor specificities are produced All necessary receptor specificities are produced Takes place in the primary (central) lymphoid organs Takes place in the primary (central) lymphoid organs Results in immature but immunocompetent T and B cells Results in immature but immunocompetent T and B cells Primarily occurs in the fetus Primarily occurs in the fetus

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 45 Clonal Selection Immunocompetent T and B cells migrate from the primary to the secondary lymphoid organs to await antigen Immunocompetent T and B cells migrate from the primary to the secondary lymphoid organs to await antigen Primarily after birth Primarily after birth Clonal selection is initiated by antigen Clonal selection is initiated by antigen Final products Final products Plasma cells that produce antibody, effector cells that help Th, Tc, or Treg, and memory B and T cells Plasma cells that produce antibody, effector cells that help Th, Tc, or Treg, and memory B and T cells

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 46 T-Cell Maturation The thymus is the central lymphoid organ of T cell development The thymus is the central lymphoid organ of T cell development T cells move from thymic cortex to the medulla T cells move from thymic cortex to the medulla Changes Changes Development of the T cell receptors and expression of surface molecules Development of the T cell receptors and expression of surface molecules T cells are released into the blood and take up residence in the secondary lymph organs T cells are released into the blood and take up residence in the secondary lymph organs

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 47 The Immune Response Process Antigen processing Antigen processing Clonal selection Clonal selection Mounting a defense against the foreign antigen Mounting a defense against the foreign antigen Production of memory cells Production of memory cells

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 48 Antigen Processing and Presentation Antigens require processing and presentation by APCs Antigens require processing and presentation by APCs Dendritic cells, macrophages, B lymphocytes Dendritic cells, macrophages, B lymphocytes For this to occur, antigen must be the appropriate type, the lymphocytes must recognize the presented antigen, and the antigen must be presented appropriately For this to occur, antigen must be the appropriate type, the lymphocytes must recognize the presented antigen, and the antigen must be presented appropriately

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 51 Helper T Lymphocytes Help the antigen-driven maturation of B and T cells Help the antigen-driven maturation of B and T cells Facilitate and magnify the interaction between APCs and immunocompetent lymphocytes Facilitate and magnify the interaction between APCs and immunocompetent lymphocytes Steps Steps Th interacts through antigen-specific and antigen- independent mechanisms Th interacts through antigen-specific and antigen- independent mechanisms Undergoes differentiation Undergoes differentiation Mature Th interacts with plasma or T-effector cells Mature Th interacts with plasma or T-effector cells

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 52 Helper T Lymphocytes Subsets Subsets Th1 cells provide help in developing cell-mediated immunity Th1 cells provide help in developing cell-mediated immunity Th2 cells provide help in developing humoral immunity Th2 cells provide help in developing humoral immunity Differences based on cytokine production Differences based on cytokine production

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 53 B-Cell Activation When an immunocompetent B cell encounters an antigen for the first time, B cells with specific BCRs are stimulated to differentiate and proliferate When an immunocompetent B cell encounters an antigen for the first time, B cells with specific BCRs are stimulated to differentiate and proliferate Differentiated B cell becomes a plasma cell Differentiated B cell becomes a plasma cell A plasma cell is a factory for antibody production A plasma cell is a factory for antibody production Single class or subclass of antibody Single class or subclass of antibody

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 54 B-Cell Activation Antibody class switch Antibody class switch Major component of B cell maturation Major component of B cell maturation During clonal selection B cell can change class of Ab (IgG, IgA, IgE) During clonal selection B cell can change class of Ab (IgG, IgA, IgE) DNA cut then mended DNA cut then mended Specificity maintained Specificity maintained

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 56 Primary and Secondary Responses Primary response Primary response Initial exposure Initial exposure Latent period or lag phase Latent period or lag phase B-cell differentiation is occurring B-cell differentiation is occurring After 5 to 7 days, an IgM antibody for a specific antigen is detected After 5 to 7 days, an IgM antibody for a specific antigen is detected An IgG response equal or slightly less follows the IgM response An IgG response equal or slightly less follows the IgM response

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 57 Primary and Secondary Responses Secondary response Secondary response More rapid More rapid Larger amounts of antibody are produced Larger amounts of antibody are produced Rapidity is due to the presence of memory cells that do not have to differentiate Rapidity is due to the presence of memory cells that do not have to differentiate IgM is produced in similar quantities to the primary response, but IgG is produced in considerably greater numbers IgM is produced in similar quantities to the primary response, but IgG is produced in considerably greater numbers

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 58 Class Switch Immunocompetent B cells use IgM and IgD as receptors Immunocompetent B cells use IgM and IgD as receptors During clonal selection, B cells have the option of changing the class of the antibody During clonal selection, B cells have the option of changing the class of the antibody One of four IgGs, one of two IgAs, IgE, or an IgM in a pentamer form One of four IgGs, one of two IgAs, IgE, or an IgM in a pentamer form DNA rearrangement DNA rearrangement

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 60 T Cell Activation Binding antigen to T cell receptors Binding antigen to T cell receptors Allows: Allows: Direct killing of foreign or abnormal cells Direct killing of foreign or abnormal cells Assistance or activation of other cells Assistance or activation of other cells T regulatory cells (Treg) T regulatory cells (Treg) Regulate the immune response to avoid attacking self Regulate the immune response to avoid attacking self Memory T cells Memory T cells

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 62 T Cell Activation T regulatory cells (Tregs) T regulatory cells (Tregs) (previously called T suppressor cells) To avoid overactivation of immune system To avoid overactivation of immune system To avoid attacking self-antigens To avoid attacking self-antigens Subject of much research Subject of much research

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 63 Antibody Function Direct Direct Neutralization Neutralization Agglutination Agglutination Precipitation Precipitation Indirect Indirect Opsonization Opsonization Degree of antibody protection is assessed by an antibody titer Degree of antibody protection is assessed by an antibody titer

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 68 Cell-Killing Mechanisms Cytotoxic T lymphocytes Cytotoxic T lymphocytes Destroy cancer cells or cells infected with virus Destroy cancer cells or cells infected with virus Perforin, granzymes, or direct receptor interactions Perforin, granzymes, or direct receptor interactions

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 69 Other Cells Natural killer (NK) cells Natural killer (NK) cells Complement Tc cell mechanisms Complement Tc cell mechanisms Tregs Tregs Provide peripheral tolerance Provide peripheral tolerance Affect recognition of antigen and suppress proliferative steps of antigen recognition Affect recognition of antigen and suppress proliferative steps of antigen recognition

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 71 Fetal and Neonatal Immunity Antibody function is deficient Antibody function is deficient Capable of primary IgM response; unable to produce an IgG challenge Capable of primary IgM response; unable to produce an IgG challenge Immunity provided by maternal antibody Immunity provided by maternal antibody Trophoblastic cells transport maternal IgG across the placenta Trophoblastic cells transport maternal IgG across the placenta Newborn IgG levels are near adult levels Newborn IgG levels are near adult levels

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 73 Aging and Immune Function Decreased T cell activity Decreased T cell activity Thymic size is 15% of its maximum size Thymic size is 15% of its maximum size Decreased production of specific antibodies Decreased production of specific antibodies Increase in circulating antigen-antibody complexes Increase in circulating antigen-antibody complexes Increase in circulating autoantibodies Increase in circulating autoantibodies Decrease in circulating memory B cells Decrease in circulating memory B cells

Adaptive Immunity Chapter 7 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.

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Adaptive Immunity Chapter 7 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.

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